During the conversion of hepato-carcinogenic amines to excretable metabolites in liver cells, reactive electrophilic species may be generated which bind to protein and nucleotide bases, causing structural and functional disturbances, which may induce cancerous states. The primary objective of this research is to test the hypothesis that the reactive electrophilic intermediate directly responsible for the cancer-inducing action of carcinogenic amines is generated in a reaction subsequent to the information of N-hydroxylated amine metabolites. Hydroxylamines will be generated in liver homogenates by the hepato-enzymatic reduction of keto-oximes under anaerobic conditions. The hepatic oxime-reductase will be characterized and partially purified. Isotopically-labelled (radioactive) oxime substrates will be incubated with liver homogenates under anaerobic conditions to determine if hydroxylamines, generated during enzymic reduction reactions, can generate electrophilic alkylating species capable of binding with protein and polynucleotide bases. Studies will also be conducted to determine if oximes and/or their metabolic intermediates effect protein and polynucleotide biosynthesis by studying their effect on the incorporation of radioactively labelled amino acids into liver slices. Similarly, their effect on the rate of incorporation of isotopically-labelled orotic acid into RNA will be studied. The oxidative metabolism of keto-oximes will concurrently be investigated, in light of recent findings that oximes are generated during the metabolism of amphetamine and other primary amines.